Sildenafil to Reduce Vascular Remodeling During Left Ventricular Assist Device Support

Pulse wave velocity (PWV) will be measured by vascular ultrasound. PWV will be calculated by dividing the distance between the carotid and femoral artery waveform acquisition sites (in meters) by the carotid-femoral transit time (change in time, in seconds). Change in group mean PWV from baseline will be summarized. Increases in PWV can be an indicator of vascular fibrosis and are associated with increased risk of cardiovascular comorbidities.

Microvascular angiodysplasia will be assessed by video capsule endoscopy (VCE). VCE is a minimally invasive technique used to identify gastrointestinal lesions and diagnose GIAD. Change in the group mean number of GIAD foci/lesions per patient from baseline to 180 days will be determined.

GIAD formation will only be assessed at baseline and at 180 days unless the patient(s) experiences an episode of gastrointestinal bleeding prior to 180 days.

Endothelial function will be determined by the finger vascular reactivity index (VRI) during LVAD support. VRI will be assessed by a non-invasive method using the Endothelix device. VRI is determined by measuring fingertip temperature change before and after cuff deflation. Change in group median VRI values from baseline will be summarized. Positive changes from baseline are associated with improved endothelial function.

Urine samples will be assessed to determine the protein to creatinine ratio. Urinary PCR is calculated by dividing the concentration of protein (mg/dL) in the urine sample by the creatinine concentration (mg/dL). Change in group mean urinary protein to creatine ratios from baseline will be summarized. Elevated ratios of protein to creatinine are associated with increased risk of renal disease and microvascular dysfunction.

Platelet samples will be assessed for changes in gene expression using RNA sequencing analysis. Platelets will be isolated from whole blood samples collected at baseline, 3 months, and 6 months from participants in each group. Equal number of isolated platelets will be lysed in Trizol and DNAse treated total RNA will be isolated. RNA sequencing will be performed using HiSeq 50 Cycle Single Read Sequencing after library preparation. Differentially expressed genes (DEGs) will be ranked by their expression change between groups. DEGs with > 1.5-fold change in expression after LVAD at a sequence depth of >30 million reads per sample will be ranked by study arm.